Esomeprazole, the S-isomer of omeprazole, is a second-generation proton pump inhibitor widely used for acid-related diseases of the oesophagus, stomach, and duodenum (peptic ulcer, gastro-oesophageal reflux disease, etc.). Studies on esomeprazole safety and toxicokinetics (TK) are essential for increasing the number of modified-release esomeprazole products manufactured in Russia.The aim of the study was to compare the safety and toxicokinetics of a new esomeprazole product, 40 mg modifiedrelease capsules (Valenta Pharm JSC, Russia), and Nexium® 40 mg film-coated tablets (AstraZeneca AB, Sweden).Materials and methods. This toxicity study involved oral administration of esomeprazole 40 mg modified-release capsules (Valenta Pharm JSC, Russia) and Nexium® 40 mg film-coated tablets (AstraZeneca AB, Sweden) to 5 groups of rabbits (8 males and 8 females per group) for 28 days at a dose of 1 or 3 capsules, or tablets, corresponding to approximately 4.8 or 14.3 maximum human therapeutic doses (MHTDs), respectively. Comparisons included general toxicity, local tolerance, safety pharmacology, effects on immune system organs, reproductive toxicity, and basic TK parameters (Cmax, Tmax, AUC0-24, MRT, and T1/2).Results. No toxic effects, including local irritation and immunotoxicity, were observed for the test product. The safety pharmacology testing demonstrated the safety of repeated oral administration of the test product for the cardiovascular, excretory, respiratory systems and the liver. The test product did not affect the reproductive system of male and female rabbits. The No Observed Adverse Effect Level (NOAEL) was determined to be 14.3 MHTDs. According to the TK parameters evaluated after single and repeated oral administration, the test product and Nexium® demonstrated comparable TK profiles.Conclusions. The study demonstrated a favourable safety profile for the test product. All the test product parameters studied were comparable with those of Nexium®. Positive clinical experience with Nexium® supports the data obtained for the new esomeprazole product. Thea safety of these medicinal products may be considered similar.

Chondroitin sulfate is used for osteoarthritis combination therapy. It should be taken into account that the structure and properties of polysaccharides included in chondroitin sulfate, as well as the raw materials used for its production, have a significant effect on its absorption, bioavailability, and, as a consequence, on the safety and efficacy of orally administered products.The aim of the study was to assess toxic properties, local irritant effect, immunotoxicity, basic pharmacokinetic parameters, and therapeutic efficacy of the new Chondroitin sulfate product (produced by Federal State Unitary Enterprise “Moscow Endocrine Plant”, Russia) as compared to Structum (produced by “Pierre Fabre Medicament Production”, France).Materials and methods: White Giant rabbits were used in the experiments. Toxicity, immunotoxicity and local irritation effects of the products were assessed following daily oral administration at the dose of 168 mg/kg (about 6 Maximum Recommended Therapeutic Doses) to male and female rabbits for 28 days. The follow-up period was 14 days. The pharmacokinetic study included blood sampling on days 1‒2 of the experiment, complete blood count and blood chemistry tests were performed on days 28 and 43. After killing the animals, pathomorphological and histological examinations were performed on their organs and tissues. Therapeutic efficacy was studied in an osteoarthritis model made by cruciate ligament transaction in rabbits. The animals received therapy at doses of 16.8 mg/kg, 33.6 mg/kg, and 67.2 mg/kg for 56 days starting from day 8 after the pathology induction.Results: the medicines had no toxic, local irritant, or immunotoxic effect. The NOAEL was established at 168 mg/kg. The study demonstrated the comparability of the pharmacokinetic profiles of the studied products following single oral administration. The maximum concentration of the active ingredient (Cmax = 79 ± 6 μg/mL—Chondroitin sulfate; Cmax = 71 ± 4 μg/mL— Structum) in blood plasma was observed within 3–4 hours after administration. A decrease in the severity of cartilage structural damage was observed for the doses of 33.6 mg/kg and 67.2 mg/kg. The results of quantitative determination of sulfated glycosaminoglicans in the proteoglycans of the cartilage articular surface in the animals with osteoarthritis demonstrated an increase in the level of sulfated glycosaminoglicans in the groups treated with the maximum doses of the studied products, as compared to the other groups.Conclusions: the obtained data confirm that the test product has a favourable safety profile, and therapeutic (chondroprotective) effect. All the tested properties of Chondroitin sulfate were comparable to those of Structum.

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Bowel-cleansing PEG-based agents, including Moviprep®, are commonly used to prepare the large intestine for diagnostic examinations. PLNV-next is a newly developed fixed combination medicinal product with a composition similar to that of Moviprep®.The aim of the study was to estimate the pharmacological efficacy and toxicity of PLNV-next.Materials and methods: The study evaluated pharmacological efficacy of four formulations of PLNV-next in comparison with Moviprep® after a single administration in a therapeutic dose to outbred rats. The evaluation was carried out based on the laxative effect of the medicinal products. The authors recorded diarrhoea onset latency and the number of defecation boluses and diarrhoea spots produced during the 6-hour observation period. Toxicity of PLNV-next was studied in the formulation containing maximum amounts of the ingredients according to the patent. In the single-dose toxicity study, PLNV-next was administered intragastrically to rats at doses of 4.2 g/kg (maximum human therapeutic dose, MHTD), 21 g/kg (5 MHTD), and 42 g/kg (10 MHTD) and to ferrets at doses of 4.2 g/kg (MHTD) and 21 g/kg (5 MHTD). In the repeated-dose toxicity study, PLNV-next was administered for 14 days at 4.2 g/kg (rats and ferrets), 21 g/kg (5 MHTD, rats), and 12.6 g/kg (3 MHTD, ferrets). Additionally, the repeated-dose toxicity study evaluated safety pharmacology parameters for the cardio-vascular, respiratory and central nervous systems.Results: All PLNV-next formulations tested exerted a laxative effect equivalent to that of Moviprep®. No clinical signs of toxicity were observed in rats, with the exception of the laxative effect. Ferrets demonstrated decreased behavioral activity and diarrhoea. Nausea or emesis were noted in 75–90% of the ferrets receiving the doses exceeding the MHTD. A single administration of PLNV-next affected blood sodium concentrations: a slight increase was noted in the 5 MHTD and 10 MHTD groups of rats and in the 5 MHTD group of ferrets. The repeated-dose toxicity study in rats revealed a slight increase in sodium levels with both test doses. After a single administration of 5 MHTD to ferrets, the authors observed a decrease in potassium levels. All the changes were mild and within physiological ranges. PLNV-next toxic effects observed in the rat and ferret studies were similar to those reported in rat and dog toxicity studies of Moviprep®. Conclusion: PLNV-next exerts a marked laxative effect and has a favourable safety profile.